Non-hodgkin lymphoma – causes, symptoms, diagnosis, treatment, pathology

Non-hodgkin lymphoma – causes, symptoms, diagnosis, treatment, pathology

The term non-Hodgkin lymphoma, sometimes called
NHL, can be broken down. Lymph- refers to lymphocytes and oma- refers
to a tumor. “Non-Hodgkin” refers to the absence of
a key cell that’s seen in Hodgkin lymphoma, the Reed-Sternberg cell. So, non-Hodgkin lymphoma is a tumor derived
from lymphocytes – specifically B-cells and T-cells, which mainly live in the lymph nodes
and move through the blood and lymphatic system. Now, B-cell development begins in the bone
marrow, which is a primary lymphoid organ. That’s where young precursor B-cells mature
into naive B-cells. The naive B cells then leave the bone marrow
and circulate in the blood and eventually settle down in lymph nodes. Humans have hundreds of lymph nodes, scattered
throughout the body, and they’re considered secondary lymphoid organs. Each lymph node has B-cells which group together
in follicles in the cortex or outer part of the lymph node, along with T-cells in the
paracortex just below the cortex. B-cells differentiate into plasma cells, which
are found in the medulla or center of the lymph node. Plasma cells release antibodies or immunoglobulins. Antibodies bind to pathogens like viruses
and bacteria, to help destroy or remove them. Various immune cells, including B-cells have
surface proteins or markers that are called CD, short for cluster of differentiation,
along with a number – like CD19 or CD21. In fact, the combination of surface proteins
that are on an immune cell works a bit like an ID card. Now, a B cell is activated when it encounters
an antigen that binds just perfectly to its surface immunoglobulin. Some of these activated B-cells mature directly
into plasma cells and produce IgM antibodies. Other activated B-cells go to the center of
a primary follicle in the lymph node and they differentiate into B-cells called centroblasts
and start to proliferate or divide. These proliferating centroblasts form a germinal
center, located in the center of the follicle of the lymph node. These centroblasts have a rearrangement of
their immunoglobulin genes, and some of them undergo a class switch where they change from
producing IgM antibodies to producing IgG or IgA antibodies. Within the germinal center, centroblasts mature
into centrocytes; and the centrocytes that make antibody with high affinity for the antigen,
differentiate into either plasma cells which go to the medulla or memory B-cells which
circulate in the blood and reside in lymph nodes, spleen, and mucosa-associated lymphoid
tissue, also called MALT. Now, T-cell development starts in the thymus
from precursors that arise in the bone marrow. In the thymus, these precursor T-cells mature
and express either CD4 on helper T-cells or CD8 on cytotoxic T-cells sometimes known as
suppressor T cells. Mature T-cells circulate in the blood and
are found in the paracortex of the lymph nodes. Generally speaking, lymphomas are grouped
into two categories. The first category is Hodgkin lymphomas which
tend to spread in a contiguous manner, rarely involve extranodal sites, and have distinctive
Reed-Sternberg cells. The second category is non-Hodgkin lymphomas
which tend to spread non-contiguously, can involve extranodal sites like the skin, gastrointestinal
tract, and the brain, and don’t usually contain Reed-Sternberg cells. In non Hodgkin lymphoma, there is usually
a genetic mutation in a lymphocyte – either a B cell or a T cell. When something like that happens, cells are
supposed to undergo apoptosis – or programmed cell death, but instead the lymphocyte starts
to divide uncontrollably – becoming a neoplastic cell. Usually, lymphomas develop in lymph nodes
and they’re called nodal lymphomas. Lymphomas can happen anywhere in the body,
though, and when they develop in other tissues or organs – like the stomach or skin – they’re
called extranodal lymphomas. Lymphoma cells can also get into the blood
and can spread to other parts of the body. If lymphoma cells get into the gastrointestinal
tract they can grow and cause bowel obstruction. If they go to the bone marrow, they can crowd
out normal bone marrow progenitor cells and decrease the number of healthy red blood cells,
white blood cells and platelets. If they go to the spinal cord they can cause
spinal cord compression. Now, the two main groups of Non-Hodgkin lymphomas
are B cell and T cell lymphomas. B cell lymphomas are more common and the neoplastic
B cells usually express CD20 on their surface. And there are various types of B cell lymphomas
and an important feature is how quickly each one grows- they can be indolent or slow to
grow, aggressive, or highly aggressive. The first type of B cell lymphoma is a diffuse
large B cell lymphoma, this type is the most common and it’s an aggressive lymphoma. A second type of B cell lymphoma is a follicular
lymphoma, and it’s an indolent lymphoma. One known mechanism for how a follicular lymphoma
develops, is a chromosomal translocation between chromosome 14 and chromosome 18. In the translocation, the two chromosomes
swap large pieces of chromosome with each other. As a result an the BCL2 gene from chromosome
18 is placed after the immunoglobulin heavy chain promoter on chromosome 14, and that
results in overexpression of bcl-2. Bcl-2 normally blocks cell death, or apoptosis,
so overexpression of the bcl-2 gene prevents the cell from dying. A third type of B cell lymphoma is Burkitt
lymphoma, and it’s a highly aggressive lymphoma. Burkitt lymphoma can also result from a chromosomal
translocation. In this case, the Myc gene is translocated
from chromosome 8 where it ends up adjacent to IgH promoter on chromosome 14 and again
that upregulates its expression. The Myc gene stimulates cell growth and metabolism,
so the translocation results in increased cell division. In individuals in Africa, Burkitt lymphoma
classically causes extranodal involvement of the jaw and is often associated with Epstein
Barr virus infection. In contrast, in individuals outside Africa,
Burkitt lymphoma classically causes extranodal involvement of the abdomen – most often at
the ileocecal junction – and is less frequently associated with Epstein Barr virus infection. Epstein Barr virus infects lymphocytes and
can incorporate its DNA into a host cell’s DNA, but exactly how that leads to lymphoma
is still unclear. Under the microscope, Burkitt lymphoma is
said to have a “starry sky” appearance. That’s because there are a few “tingible
bodies” which are macrophages that have eaten up dead neoplastic cells that look like
little stars. And these are scattered among lots of neoplastic
lymphocytes that look dark like the night sky. A fourth type of B cell lymphoma is mantle
cell lymphoma, and this one’s an aggressive lymphoma. Mantle cell lymphoma can also result from
a chromosomal translocation. In this case, the BCL1 gene from chromosome
11 ends up next to the immunoglobulin promoter on chromosome 14, which again upregulates
its expression. The BCL1 gene encodes the protein cyclin D1,
which stimulates cell growth, so once again the translocation results in increased cell
division. A fifth type of B cell lymphoma is marginal
zone lymphoma, and it’s an indolent lymphoma. The most common type is marginal zone lymphoma
of mucosa-associated lymphoid tissue or MALT. This type is extranodal – mostly happening
in the lining of the stomach among individuals with chronic inflammation, like those with
Helicobacter pylori infection, a bacteria that causes chronic gastritis. There’s also nodal marginal zone lymphoma,
which happens within lymph nodes, and splenic marginal zone lymphoma which happens in the
spleen. A sixth type of B cell lymphoma is lymphoplasmacytic
lymphoma, and this one’s also an indolent lymphoma. This form of lymphoma often involves the bone
marrow, lymph nodes, and spleen, and the neoplastic cells sometimes produces immunoglobulins,
called “M proteins,” that are found at high levels in the blood. When this happens, the additional proteins
in the blood cause the blood to be more thick and viscous and the condition is called Waldenstrom
macroglobulinemia. The other group of non Hodgkin lymphomas are
the T cell lymphomas. The first T cell lymphoma is adult T-cell
lymphoma, but it’s sometimes referred to as a leukemia because the abnormal white blood
cells or leukocytes often get into the bloodstream. Adult T-cell lymphoma is thought to be caused
by the human T-lymphotropic virus or HTLV, which spreads through body fluids and infects
T cells. HTLV incorporates its DNA into T cell DNA
and causes a genetic mutation in the process, and that leads to adult T-cell lymphoma. The second T cell lymphoma is mycosis fungoides
which is a T cell lymphoma of the skin that causes patches on the skin that looks a bit
like a fungal infection. The neoplastic cell in mycosis fungoides is
a CD4+ helper T-cell, and under a microscope it has a distinctive “cerebriform” nucleus
because it looks like a brain. If these neoplastic CD4+ helper T-cells start
to circulate in the blood, they can cause Sezary syndrome, which is when there’s a
generalized red rash called erythroderma or itchy skin. For symptoms, Individuals with non-Hodgkin
lymphoma usually develop painless lymphadenopathy. The release of cytokines causes symptoms like
fever, drenching night sweats, and weight loss. If there’s extranodal involvement of the
gastrointestinal tract, it can cause bowel obstruction. If there’s extranodal involvement of the
bone marrow, it can cause fatigue, easy bruising, or recurrent infections. And if there’s extranodal involvement of
the spinal cord, it can cause weakness and a loss of sensation – usually in the legs. Identifying non Hodgkin lymphoma often begins
with imaging studies, like a CT scan, which can help establish the stage of the lymphoma. The staging is based on the extent of nodal
and extranodal involvement. And finally a lymph node biopsy is required
for diagnosis. Treatment options for non-Hodgkin lymphoma
mainly consists of chemotherapy and radiation therapy, and depend on things like the lymphoma
subtype, whether it’s indolent, aggressive, or highly aggressive, and how far it has spread. If the lymphoma has CD20-positive B-cells,
Rituximab can also be used. Rituximab is a monoclonal antibody that binds
CD20 and induces complement-mediated lysis, as well as direct cytotoxicity and apoptosis. All right, as a quick recap, non-Hodgkin refers
to the absence of “Reed-sternberg cells” which are characteristic of hodgkin lymphoma. Non-hodgkin lymphomas can originate from B
cells or T cells, though they most commonly arise from B cells. Diffuse large B-cell lymphoma is the most
common type of non-Hodgkin lymphoma among adults, and follicular lymphoma is the most
common indolent or slow-growing non-hodgkin lymphoma. T cell lymphomas include adult T-cell lymphoma,
which is sometimes referred to as leukemia, as well as mycosis fungoides.


100 thoughts on “Non-hodgkin lymphoma – causes, symptoms, diagnosis, treatment, pathology”

  • FINALLY….just 2 weeks before my Pathology exam! Please hurry and make videos on Hodgkin lymphoma, gastric cancer, endometrial carcinoma, ovarian and testicular carcinomas, and a few videos on bone and joint disorders would be nice too.

  • Anand Sasidharan says:

    Excellent presentation and content. But it would have been more useful for the beginners if there was a little more brief discussion on anatomy of lymph node.. like where is marginal zone , mantle zone germinal center and all,. ..

  • Илес Заудинов says:

    This feeling… When you are from Russia and don’t understand English perfectly. But you got this theme more clearly from this video than from your’s f*cking pathology book. Спасибо!

  • Could DNA damage repair mechanisms be reprogrammed in a way that its injectable to a cancerous site, searches for known DNA abnormalities (Like a Computer Virus Scan using its Database of known viruses, worms, trojans), release a chemical to weaken the host cell and trigger the immune system to attack this cell relentlessly?

    Was always wondering if DNA based diseases had a sort of "Base Code" you could go off of for identifying it and maybe in the future targeting in on it.

  • Please Give Link To Your Video's Script , I See Some Video's Well Written Script Available In Wikipedia But not All So Please Give Link Of Video in Comments

  • Loving your videos so much. Can you make a video about rheumatoid arthritis. Its also very important one 😀 and if u do it soon as much as it can be ill be happy 😛

  • Omg!! much awaited video!!! Thank you so much Osmosis for this. This made my Pathology exam preparation so easier. Thanks a lot. This channel is just a blessing to my studies😄😄 waiting for new videos!!

  • We need a video on Hodgkin’s lymphoma too!!! I came here for the acute leukaemia video which led me to chronic leukaemia and I’ve been so glad I found these videos!! please please make one on Hodgkin’s lymphoma!

  • This is the best that I have seen. I am on my third time with NHL (1998 -2010 – now 2018). Please don't expect your oncologist to explain what kind that you have, and yes you can have several kinds at the same time. Spleen out the first time, and chemo each time and now.

  • My sister was diagnosed with lymphoma a few years ago. Thankfully, she beat the disease and is now working hard to ensure that a cure for all blood cancers are found. I'm a part of her team that's raising money for the Leukemia and Lymphoma Society. We're trying to raise as much money as possible between now and May 19th. If you'd like to contribute to blood cancer research, please consider clicking on the following link. Thank you!

  • Mustafa Kadhim says:

    Now when they say that lymphoma can appear in the GIT or skin,, do they mean the MALT there or the mucosa as a secondary metastasis? or both?

  • adam david kenyon says:

    I live in UK, my sweet Mum just died two weeks ago from this fucking awful cruel disease. I am completely destroyed by this, I loved her so much, she was my best friend as well. I cared for her for two years. Two years of itching, painful red skin, infections, gashes in her legs with swelling and puss, hair loss from scratching, puss in eyes from the scurf from the head falling into her eyes, weak bones. I watched my lovely Mum deteriorate into nothing….Fuck the NHS, kept telling us for a year that it was Psoriasis when it was actually the rare cancer, Cutaneous T cell Non Hodgkin Lympthoma. A disease that puts you at high risk of infection, she was admitted to hospital five weeks ago when going for a routine appointment, they told her she had MSRA and said she could go home soon with antibiotics, then it turned bad. It turned into Pneumonia, which got worse and turned into extreme Pneumonia in her final hours. Sending her into a coma because of breathing complications, basically brain dead and full body organ failure.

    She didn't deserve this! She was the loveliest person in the world and put everyone else first before her. I feel so lost…..I feel angry that her diagnosis was delayed time after time. All she needed was a lumbar punch and that proved that she had early stage cancer, but they decided to leave it till stage 3 to find out. We kept being told the cancer had not metastasised but it had spread to her lungs months ago. I cry when I think about the horror she has been through and when she kept telling me on the phone her dreams/plans for future, that she wanted to come home. I feel like I couldn't protect her. She died suffocating with water on her lungs. DO not let your diagnosis go unheard, get this checked out people, we didn't know any better. It can show up as Psoriasis or Dermatitis, this video does not explain that. There is no known cause to this disease, it is rare and a genetic mutation with no known cause other than age related.

    There is NO cure for it. Until Immunotherapy gets better, there is nothing that can be done. It is just controlled and very hard to get into remission. Being a blood cancer, it's everywhere, hers was low grade so slow growing, and much harder to treat. There needs to more awareness and money raised for this disease.

  • Oasis you all are great, i really wished you continued the other t cell lymphomas though other than the 1st 2 examples.
    IS IT POSSIBLE FOR YOU GUYS TO DO THE REST PLEASEEEEEEEEEE. Such as "Large Granular Lymphocytic Leukemia" and "Extranodal NK/T-Cell Lymphoma"

  • Love the info. I had Infused LG B cell non Hoskins lymphoma. It's been 6 months since my chemo. I had R-CHOP. Doing pretty good. Still a bit tierd.

  • I just want to say I wish I have known your channel earlier. A lot of these diseases you mention are compressed down to only 12 minutes video but make a lot more sense than 100 slides of medical lecture. Thank you.

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    I work in possessed man with irresistible force furiously.

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  • A video on Hodgkin lymphoma please which is a regional type,with , low cell mediated immunity by EBV AND Hiv,types are Nodular sclerosis,lym predom,lym dep,mixed cellularity…

  • mustafa cem cemaligil says:

    Where? Where is the golden heart of our reign; we're trying to find the golden heart of our reign. We are digging more and more deeper while we're bearing the burden of entire earth. Where is the narrator of video Amyloidosis? We are waiting for her in despair. Destiny still arrives.

  • Mantle cell lymphoma is low grade lymphoma yet with the worst prognosis of all. But is it aggressive when it’s low grade?

  • At 3:09 Cytotoxic t-cell is not the same as suppressor t-cell; it is regulatory t-cell that is sometimes known as suppressor t-cell.

  • The diagnosed in Africa can survive very well if they get treatment which means Burkitt is not aggressively deadly. It's fast but very treatable.

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